The role of the regional lymph node (RLN) in the host response to tumor has been studied to aid in formulating therapeutic regimes. Data has been obtained concerning (a) the effect of a second asynchronous tumor focus on regional and distant lymph node cell (RLNC and NRLNC) cytotoxicity elicited by a primary tumor, (b) the influence of a pre- existing tumor on cytotoxicity expected as a result of such a second implant, and (c) the cytotoxicity of RLNCs and NRLNCs in response to a second tumor challenge at various time intervals following removal of a primary tumor. Very briefly, our investigations indicate (a) that while a primary tumor was present maximal cytotoxicity was displayed only by cells from nodes regional to that tumor. NRLNs could not be induced to display cytotoxicity of a similar magnitude even when they were directly exposed to a second tumor challenge; (b) cells from NRLNs which failed to demonstrate an increased cytotoxicity upon exposure to a subsequent tumor focus, were capable of demonstrating such activity when the second challenge occurred following removal of the primary tumor. Cells from nodes regional to a primary tumor rapidly lost their cytotoxicity following removal of the primary tumor and with passage of time were unable to regain that function in response to a subsequent second tumor focus whereas NRLNs failed to demonstrate this phenomenon; (c) Evidence presented demonstrated that C. parvum administered to tumor bearing animals augments in vitro cytotoxicity of RLNCs and NRLNCs. During the coming year efforts will be directed toward (a) relating changes of cell type in LNs as a result of treatment of cytotoxicity, (b) identifying the cell type responsible for cytotoxicity and (c) correlating effectiveness of therapy with changes in cell type occurring in LNs as a result of the therapy.